Huhs1015 downregulates pkm2 through an ampk/p38mapk pathway in mkn45 cells

In the earlier study, the newly synthesized anticancer drug HUHS1015 decreased pyruvate kinase M2 (PKM2) in MKN45 human gastric cancer cells due to autophagic degradation. The present study was conducted to gain further insight into the mechanism underlying HUHS105-induced autophagic degradation of PKM2. HUHS1015 phosphorylated at Thr172 and activated AMP-activated protein kinase (AMPK). HUHS1015, alternatively, phosphorylated at Thr180/Tyr182 and activated p38 mitogen-activated protein kinase (p38MAPK). HUHS1015-induced decrease of PKM2 was cancelled by the AMPK inhibitor Compound C or combination of the MAP kinase kinase (MAP2K) inhibitor PD98059 and the p38MAPK inhibitor SB203580. Taken together, these results indicate that HUHS1015 activates AMPK and the effector p38MAPK, which triggers autophagic degradation, to decrease PKM2 in MKN45 cells.